Arizona Health Sciences

A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals.

TitleA single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals.
Publication TypeJournal Article
Year of Publication2016
AuthorsHingorani DV, Montano LA, Randtke EA, Lee YSun, Cárdenas-Rodríguez J, Pagel MD
JournalContrast Media Mol Imaging
Volume11
Issue2
Pagination130-8
Date Published2016 Mar-Apr
ISSN1555-4317
KeywordsAmides, Amines, Catalysis, Cathepsin B, Contrast Media, Ligands, Magnetic Resonance Imaging, Molecular Imaging, Water
Abstract

CatalyCEST MRI can detect enzyme activity by monitoring the change in chemical exchange with water after a contrast agent is cleaved by an enzyme. Often these molecules use paramagnetic metals and are delivered with an additional non-responsive reference molecule. To improve this approach for molecular imaging, a single diamagnetic agent with enzyme-responsive and enzyme-unresponsive CEST signals was synthesized and characterized. The CEST signal from the aryl amide disappeared after cleavage of a dipeptidyl ligand with cathepsin B, while a salicylic acid moiety was largely unresponsive to enzyme activity. The ratiometric comparison of the two CEST signals from the same agent allowed for concentration independent measurements of enzyme activity. The chemical exchange rate of the salicylic acid moiety was unchanged after enzyme catalysis, which further validated that this moiety was enzyme-unresponsive. The temperature dependence of the chemical exchange rate of the salicylic acid moiety was non-Arrhenius, suggesting a two-step chemical exchange mechanism for salicylic acid. The good detection sensitivity at low saturation power facilitates clinical translation, along with the potentially low toxicity of a non-metallic MRI contrast agent. The modular design of the agent constitutes a platform technology that expands the variety of agents that may be employed by catalyCEST MRI for molecular imaging.

DOI10.1002/cmmi.1672
Alternate JournalContrast Media Mol Imaging
PubMed ID26633584
PubMed Central IDPMC4882611
Grant ListR01CA167183-01 / CA / NCI NIH HHS / United States
R01 CA169774 / CA / NCI NIH HHS / United States
P50 CA095060 / CA / NCI NIH HHS / United States
R01 CA167183 / CA / NCI NIH HHS / United States
P50 CA95060 / CA / NCI NIH HHS / United States
Faculty Member Reference: 
Yeon Sun Lee, Ph.D.